A fluorescein angiography procedure for the evaluation of mean retinal circulation time will soon be a validated standard routine research procedure. Evaluation of the densities obtained on photographic film have been made by a computerized microdensitometric device that eliminates human error from these critical measurements. Clinical reproducibility studies are to be conducted in normal controls, genetic prediabetic subjects (offspring of two diabetic parents) and in juvenile diabetic patients. Data will be accumulated and appropriately analyzed to quantify the reproducibility when a fluorescein angiogram is conducted in one eye and then repeated within a two hour period of time in the same eye. In one sub-study the initial transit will be obtained while the subject is fasting and the second transit two hours post-prandially. In a second sub-series the initial transit will be obtained two hours post-prandial and a second transit after an additional two hours have elapsed. Additional studies will be conducted in normal controls and in offspring of two diabetics parents, whereby transits will be performed in the same eye on two consecutive days approximately two hours post-prandially, and in addition, a third transit will be performed in the previously studied eye 7 to 10 days after the initial transit also two hours post-prandially. In addition to these reproducibility studies, techniques for measurement of hemoglobin A1c and histocompatibility antigens are being established. Also, collaborations to allow for the evaluation of muscle capillary basement membrane thickness will soon be crystalized. The ultimate objective will be to evaluate in a prospective way the interrelationships of these various measurements to the natural course of diabetes mellitus.